Cytomegalovirus (CMV) infections transmitted by blood transfusion have become a serious problem, particularly in neonates and in adult patients with underlying immune deficiency. The mechanisms by which CMV infects and persists in blood cells are not understood, and no reliable or practical methods of screening potentially infectious blood donors have been developed. Since as many as 40-70% of normal blood donors have been previously infected with CMV, the detection of those likely to transmit the virus in transfused blood is especially important. In this proposal, an hypothesis is presented which reconciles earlier observations concerning blood transfusion and CMV infection with more recent findings. It is proposed that healthy individuals previously infected with CMV undergo periodic reactivation of latent virus which results in restimulation of the immune response and production of virus-specific IgM antibody. In this setting, humoral stimulation could result from expression of CMV antigens on the surface infected leukocytes and other cells or from release of free virus by infected cells. If an individual serves as a blood donor during spontaneous viral reactivation, CMV is more likely to be transferred to the transfusion recipient. The hypothesis will be tested by serial monitoring of blood donors for evidence of viral reactivation, including production of CMV-specific IgM, and by follow-up of blood recipients of CMV IgM-positive and CMV-IgM negative blood for evidence of CMV infection. The value of detection of CMV-specific IgM as a screening test will thus be delineated. Virus reactivation in both donors and recipients will be sought by "dot-blot" and in situ DNA hybridization using cloned DNA probes to detect viral genetic material in leukocytes. Using similar methods, the molecular events which take place during virus: leukocyte interactions in vitro will also be studied. Finally, important aspects of latent CMV infection of lymphocytes and transfusion of latent virus will be studied in a well-characterized murine model. This multifaceted approach will substantially advance the state of knowledge with respect to CMV and blood transfusion.